TFF3 expression-enhancing composition

JP2025025928APending Publication Date: 2025-02-21MEGMILK SNOW BRAND CO LTD
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Application Number
JP2023131183
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-08-10
Publication Date
2025-02-21

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Abstract

To provide a novel TFF3 expression-enhancing composition.SOLUTION: A TFF3 expression-enhancing composition comprises a sugar chain having a Lewis X structure and / or a sugar chain having a sialyl Lewis X structure as an active ingredient. The present invention also provides a TFF3 expression-enhancing pharmaceutical composition, a TFF3 expression-enhancing food composition or a TFF3 expression-enhancing feed composition, each comprising the TFF3 expression-enhancing composition. The present invention further provides an allergy disease preventing and / or improving composition comprising the TFF3 expression-enhancing composition.SELECTED DRAWING: Figure 1
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Description

[Technical field]

[0001] The present invention relates to a composition for enhancing TFF3 expression, which contains a sugar chain as an active ingredient, and also to a pharmaceutical composition, food composition, or feed composition for enhancing TFF3 expression, which contains the composition. [Background technology]

[0002] Approximately 1000 species of bacteria exist in the human intestine, and we live in symbiosis with these bacteria (intestinal bacteria). The intestinal barrier is an essential mechanism for maintaining this symbiotic relationship, and mucosal epithelial cells and immune cells separate the intestinal bacteria from the host, playing a role in maintaining homeostasis in the body. Once the intestinal barrier is disrupted, foreign substances in the intestine flow into the body and reach organs throughout the body via the blood, resulting in an inflammatory state. Therefore, disruption of the intestinal barrier is thought to be related to various diseases such as food allergies. In other words, if the intestinal barrier function can be enhanced, it is expected that it will contribute to the prevention and improvement of these diseases.

[0003] Trefoil factor 3 (hereinafter sometimes referred to as TFF3), an intestinal secretory protein, is a control factor of intestinal mucosa and antibacterial substances, which are important for maintaining the function of the intestinal barrier. TFF3 is known to contribute to strengthening mucin binding and mucosal repair. It has been reported that in intestinal epithelial cells to which TFF3 has been added, the production of inflammatory cytokines caused by LPS, an inflammation-inducing factor, is suppressed, while the expression of β-defensin (hBD2, hBD4), an antibacterial peptide, is enhanced (Non-Patent Document 1). Therefore, a component that promotes the expression and production of TFF3 can be expected to strengthen the intestinal barrier function through strengthening the intestinal mucosa and enhancing β-defensin production, and to prevent various diseases.

[0004] It has been reported that the expression of TFF3 in the intestinal tract is influenced by diet. For example, it has been reported that mice that ingested Lactobacillus rhamnosus GG and milk casein had increased TFF3 expression in the large intestine (Non-Patent Document 2). It has also been reported that when rats were fed kiwi fruit, the intestinal flora changed and TFF3 expression in the large intestine increased (Non-Patent Document 3). These reports suggest that changing the intestinal flora contributes to increased TFF3 expression. In fact, it has been reported that rats that ingested a mixture of prebiotic fructooligosaccharides and resistant starch also had increased intestinal bacteria of the Lactobacillus and Bifidobacterium genera and increased TFF3 expression (Non-Patent Document 4).

[0005] By the way, various sugar chains with physiological activity have been reported, one of which is the Lewis X sugar chain. The Lewis X sugar chain is a general term for oligosaccharides in which fucose is bound to N-acetylglucosamine of type II lactosamine at α1-3. A Lewis X sugar chain in which galactose is bound to sialic acid at α2-3 is called a sialyl Lewis X sugar chain. Glycolipids and glycoproteins with such sugar chain structures play an important role in intercellular information transmission and recognition mechanisms as cancer-related antigens. It has been reported that Lewis X sugar chains are also found in normal cells and exist in a state bound to mucin in the breast, large intestine, and oral mucosa (Non-Patent Document 5). However, this report merely confirmed the existence of Lewis X sugar chains, and did not evaluate the physiological function of the Lewis X sugar chains themselves in the intestinal tract. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] GJ Barrera, G. Sanchez, and JE Gonzalez, “Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29,” Bosn. J. Basic Med. Sci.,vol.12,no.4,pp.256-264,2012.

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[0007] An objective of the present invention is to provide a novel composition for enhancing TFF3 expression. [Means for solving the problem]

[0008] As a result of intensive research aimed at solving the above problems, the present inventors have found that sugar chains having a Lewis X structure or a sialyl Lewis X structure have an effect of enhancing TFF3 expression, and have completed the present invention. That is, the present invention is as follows. <1> A composition for enhancing TFF3 expression, comprising a sugar chain having a Lewis X structure and / or a sugar chain having a sialyl Lewis X structure as an active ingredient. <2> The glycan having a Lewis X structure is a Lewis X trisaccharide. <1> A composition for enhancing TFF3 expression described in the above. <3> The sugar chain having a sialyl Lewis X structure is 3'-sialyl Lewis X or sialyl Lewis X lactose. <1> A composition for enhancing TFF3 expression described in the above. <4> <1> from <3> A pharmaceutical composition, a food composition, or a feed composition for enhancing TFF3 expression, comprising the composition for enhancing TFF3 expression described in any one of the above. <5> <1> from <3> A composition for preventing and / or ameliorating an allergic disease, comprising a composition for enhancing TFF3 expression described in any one of the above. Effect of the Invention

[0009] According to the present invention, it is possible to provide a composition for enhancing TFF3 expression, which contains, as an active ingredient, a sugar chain having a Lewis X structure and / or a sugar chain having a sialyl Lewis X structure. It is also possible to provide a pharmaceutical composition, food composition, or feed composition for enhancing TFF3 expression, which contains the composition. [Brief description of the drawings]

[0010] [Figure 1] The figure shows the expression level of the TFF3 gene (intestinal barrier-related gene) 48 hours after adding 10 mg / ml of Lewis X sugar chain to LS174T cells, a human colonic goblet cell model. In the figure, * indicates P<0.05. [Diagram 2] The figure shows the expression level of the TFF3 gene (intestinal barrier-related gene) 48 hours after adding 5 mg / ml of sialyl Lewis X sugar chain to LS174T cells, a human colonic goblet cell model. In the figure, * indicates P<0.05. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The composition for enhancing TFF3 expression of the present invention is characterized by containing a sugar chain having a Lewis X structure and / or a sialyl Lewis X sugar chain as an active ingredient. The present invention also relates to a pharmaceutical composition, food composition, and feed composition for enhancing TFF3 expression, which contain the composition. The present invention further relates to a composition for preventing or improving allergic diseases, which contains the composition for enhancing TFF3 expression. Each active ingredient and the composition for each use will be described below.

[0012] (Lewis X sugar chain or sialyl Lewis X sugar chain) The sugar chain having a Lewis X structure, which is an active ingredient of the present invention, is a sugar chain having a Galβ1-4(Fucα1-3)GlcNAc structure in the sugar chain structure, and refers to a sugar chain having an effect of enhancing TFF3 expression. Specifically, examples include Neu5Acα2-3Galβ1-3[Galβ1-4(Fucα1-3)GlcNAcβ1-6]GalNAc, Galβ1-4(Fucα1-3)GlcNAcβ1-3GalNAc, Galβ1-4(Fucα1-3)GlcNAcβ1-3Gal, Galβ1-4(Fucα1-3)GlcNAcβ1-3Galβ1-4Glc, Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-3(Galβ1-4GlcNAcβ1-2Manα1-6)Manβ1-4GlcNAcβ1-4(Fucα1-6)GlcNAc, etc. Hereinafter, glycans having Lewis X structures are sometimes simply referred to as "Lewis X glycans".

[0013] The sugar chain having a sialyl Lewis X structure, which is an active ingredient of the present invention, refers to a sugar chain that has a Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc structure in the sugar chain structure and has the effect of enhancing TFF3 expression. Specifically, examples include Neu5Acα2-3Galβ1-3[Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-6]GalNAc, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-3GalNAc, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-3Galβ1-4Glc, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-3(Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-6)Manβ1-4GlcNAcβ1-4(Fucα1-6)GlcNAc, etc. Hereinafter, a sugar chain having a sialyl Lewis X structure may be simply referred to as a "sialyl Lewis X sugar chain".

[0014] The Lewis X sugar chain or sialyl Lewis X sugar chain of the present invention may be in a free state or bound to a peptide and / or protein. It may also be derived from milk, eggs, meat, microorganisms, or recombinant bacteria fermentation, and may be a synthetic product, semi-synthetic product, or natural product. Natural materials containing natural products may be used as a supply source and added to the nutritional composition of the present invention. Here, the term "natural product" refers to a product extracted from a natural material containing Lewis X sugar chain or sialyl Lewis X sugar chain by a known method, a crude product, or a product further purified by these methods.

[0015] The composition for enhancing TFF3 expression of the present invention preferably contains Lewis X sugar chain or sialyl Lewis X sugar chain at 3.3 μmol / 100 g solid or more, more preferably 7.8 μmol / 100 g solid or more. When the composition for enhancing TFF3 expression is added to powdered milk for infants, etc., the milk after preparation preferably contains Lewis X sugar chain or sialyl Lewis X sugar chain at 4.3 μmol / L or more, more preferably 10.1 μmol / L or more.

[0016] (How to use) As described above, the composition for enhancing TFF3 expression of the present invention can contain various sugar chains, etc. derived from milk, fermentation methods of genetically modified bacteria, synthetic products, semi-synthetic products, or natural products as active ingredients, and can therefore be widely used as raw materials for pharmaceuticals, foods, beverages, and feed.

[0017] (Pharmaceutical composition for enhancing TFF3 expression) When the composition for enhancing TFF3 expression of the present invention is formulated as a pharmaceutical product, it can be appropriately mixed with excipients, stabilizers, flavoring agents, etc. that are approved for formulation, and then concentrated and lyophilized. These dried products, concentrates, and paste-like products are also included. In addition, it can be formulated by mixing excipients, binders, disintegrants, lubricants, flavoring agents, suspending agents, coating agents, and other optional drugs within a range that does not interfere with the TFF3 expression enhancing action of various sugar chains. As for dosage forms, tablets, capsules, granules, powders, powders, syrups, etc. are possible, and these are preferably administered orally.

[0018] (Food composition for enhancing TFF3 expression) The composition for enhancing TFF3 expression of the present invention may be incorporated into any food or drink, or may be added to raw materials during the manufacturing process of the food or drink. Examples of the food or drink include, but are not limited to, dairy products such as cheese, fermented milk, dairy lactic acid bacteria beverages, lactic acid bacteria beverages, butter, margarine, etc., beverages such as milk beverages, fruit juice beverages, and soft drinks, egg products such as jelly, candy, pudding, and mayonnaise, confectionery and bread such as butter cake, and further various types of milk powder, foods for infants, and nutritional compositions.

[0019] The classification of the above-mentioned food and drink is not particularly limited, and the food and drink can be general food, health functional food, special purpose food, etc. In addition, the health functional food can be a specific health food, a nutrient functional food, a functional food, etc.

[0020] When indicating the use of the composition for enhancing TFF3 expression of the present invention, examples of the indication include indications stipulated by various laws, enforcement regulations, guidelines, etc. Indications of use include indications on packages such as wrapping and containers, as well as indications on advertising media such as pamphlets.

[0021] (Feed composition for enhancing TFF3 expression) The composition for enhancing TFF3 expression of the present invention can be added to feed. It may be added to any feed, similar to the above-mentioned foods and beverages, or may be added to the raw materials during the production process of the feed.

[0022] The subject to which the composition for enhancing TFF3 expression of the present invention is administered is not particularly limited, and may be a human or a non-human animal (e.g., a dog, a cat, a horse, or a rabbit). When the subject is a human, the composition may be administered to a minor under 18 years of age, an adult, or an elderly person over 65 years of age. Subjects to which the composition for enhancing TFF3 expression of the present invention is administered include healthy subjects and subjects diagnosed with an autoimmune disease or allergy. Further examples include subjects who have not yet developed allergic symptoms and are hoping for allergy prevention.

[0023] (Method for evaluating the effect of enhancing TFF3 expression) The TFF3 expression enhancing effect of the present invention can be evaluated by confirming whether the TFF3 expression effect is enhanced by the evaluation target component. For example, it can be evaluated by the following method using a human colon goblet cell model or the like. More details are described in the Examples. (1) A human colon goblet cell model is cultured in a medium containing the component to be evaluated. (2) Total RNA is extracted from the cultured cells using a nucleic acid extraction reagent, and cDNA is obtained. The expression levels of the TFF3 gene and the housekeeping gene 18S rRNA gene are measured for the obtained cDNA. The relative expression levels are calculated, and the TFF3 expression level is corrected by the 18S rRNA expression level. If the TFF3 expression level calculated in this manner is found to be increased when the component to be evaluated is contained compared to when it is not contained, then the component to be evaluated can be evaluated as having the effect of enhancing TFF3 expression.

[0024] (Allergy prevention effect) The composition for preventing or improving allergic diseases of the present invention is a composition containing the composition for enhancing TFF3 expression. By ingesting an effective amount of the active ingredients Lewis X sugar chain and / or sialyl Lewis X sugar chain, it has the effect of improving allergic symptoms or preventing the onset of allergic diseases. As for the mechanism of action, since TFF3 is known to comprehensively contribute to strengthening the intestinal barrier function through various actions such as strengthening mucin binding, mucosal repair, inflammation suppression, and antimicrobial peptide production induction, it is considered that the effect of preventing or improving allergies can be expected by strengthening the intestinal barrier through the action of enhancing TFF3 expression. EXAMPLES

[0025] The present invention will be described in more detail below with reference to test examples and examples, but the present invention should not be construed as being limited to these examples, etc. Unless otherwise specified, % indicates % by mass.

[0026] [Test Example 1] Evaluation of the relationship between Lewis X sugar chains or sialyl Lewis X sugar chains and intestinal barrier function In order to verify the effect of Lewis X sugar chains or sialyl Lewis X sugar chains on enhancing TFF3 expression, the following evaluation was carried out.

[0027] 1. Method (1) Cells and reagents Human colonic goblet cell model LS174T cells (EC87060401-F0) were purchased from KAC Co., Ltd. The medium used was MEM containing Earle's salts, NEAA, and L-glutamine (21443-15, Nacalai) supplemented with 10% FBS (Gibco) and 1% P / S (15140-122, Gibco). Culture was performed at 37°C and 5% CO2. Lewis X Trisaccharide (OL06490) and 3'-Sialyl Lewis X (OS04058) were purchased from Biosynth. Sialyl Lewis X-lactose (SLS0886) was purchased from Tokyo Chemical Industry Co., Ltd. Lewis X Trisaccharide is a sugar chain having a Lewis X structure, and 3'-Sialyl Lewis X and Sialyl Lewis X lactose are sugar chains having a sialyl Lewis X structure.

[0028] (2) Sample addition test to LS174T cells 1 x 10 LS174T cells 5 The cells were seeded in a 48-well plate (3830-048, AGC Technoglass Co., Ltd.) at 16.5 cells / well. After overnight incubation, the plate was washed once with PBS, and the medium was replaced with medium containing 5 or 10 mg / ml of each sample, followed by incubation for 48 hours.

[0029] (3) RNA extraction, cDNA synthesis, and gene expression measurement The cells were washed once with PBS, and total RNA was extracted using a nucleic acid extraction reagent (Maxwell® RSC simplyRNA Tissue, AS1340, Promega) and an instrument (Maxwell® RSC Instrument, Promega). The extracted total RNA was reverse transcribed using ReverTra Ace qPCR RT Master Mix (FSQ-201, Toyobo) to obtain cDNA. The expression levels of the TFF3 gene and the housekeeping gene 18S rRNA gene were measured for the obtained cDNA using THUNDERBIRD® NextSYBR® qPCR Mix (QPX-201, Toyobo) and QuantStudio 6 Pro (Therno Fisher Scientific). Standard curves were created for each gene to calculate the relative expression levels, and the TFF3 expression levels were corrected by the 18S rRNA expression levels. The primers used are shown in the table below.

[0030] [Table 1]

[0031] (4) Statistical analysis Data are shown as arithmetic mean + standard deviation. Comparison between two groups was performed using Student's t-test. Multiple comparison with the control group was performed using Dunnett's test. The significance level was set at P = 0.05.

[0032] 2.Results (1) Evaluation of the effect of Lewis X glycosylation on TFF3 expression LS174T cells, a model of human colonic goblet cells, were cultured for 48 hours after addition of 10mg / ml Lewis X (administered in the form of trisaccharide), and the expression level of TFF3 was evaluated. As a result, a significant increase in TFF3 expression was observed with the addition of Lewis X (Figure 1). In other words, it was demonstrated that Lewis X glycans have the effect of enhancing TFF3 expression.

[0033] (2) Evaluation of the effect of sialyl Lewis X and sialyl Lewis X lactose on TFF3 expression Since Lewis X glycans were found to enhance TFF3 expression, we examined the effectiveness of sialyl Lewis X and sialyl Lewis X lactose, which have structures similar to Lewis X glycans. LS174T cells were cultured for 48 hours with 5mg / ml 3'-sialyl Lewis X or sialyl Lewis X lactose, and the expression level of TFF3 was evaluated. As a result, an increasing tendency was observed with 3'-sialyl Lewis X (P=0.066), and a significant increase was observed with the addition of sialyl Lewis X lactose (Figure 2). That is, it was shown that glycans having Lewis X structures or sialyl Lewis X structures have an effect of enhancing the expression of TFF3. TFF3 is known to contribute to comprehensively strengthening the intestinal barrier function through various actions such as strengthening mucin binding, mucosal repair, inflammation suppression, and induction of antimicrobial peptide production. Therefore, it was suggested that glycans having Lewis X structures or sialyl Lewis X structures have an effect of strengthening the intestinal barrier through enhancing the expression of TFF3.

[0034] [Test Example 2] Analysis of glycoprotein glycans in human milk and pig stomach-derived mucin Glycoprotein glycans with Lewis X structures in human milk and porcine stomach mucins were analyzed.

[0035] 1. Method (1) Measurement of O-linked glycans Lewis X glycans are abundant in mucin-type glycans (O-linked glycans), so we searched for Lewis X glycans in the O-linked glycans of mucins derived from breast milk and pig stomach. For mucins derived from breast milk and pig stomach, 2-AB-labeled O-linked glycans were prepared using the O-linked glycan analysis kit EZGlyco Prep kit (Sumitomo Bakelite Co., Ltd.), and subjected to LC / MS analysis and LC / MS / MS analysis. The HPLC was performed using an UltiMate 3000 and the MS was performed using a Q-Exactive. The column used was a GlycanPac AXH-1, and the column temperature was set to 40°C. The mobile phase used was acetonitrile (liquid A) and a 50 mM ammonium formate aqueous solution (liquid B) with a pH adjusted to 4.4, and the flow rate was 0.4 mL / min. After sample introduction, the proportion of solution B was increased linearly from 10% to 35% by 55 minutes, and then solution B was passed at 35% from 55 minutes to 65 minutes. The spray voltage of the ESI probe was 3.5 kV, the capillary temperature was 275°C, and nitrogen gas was used as the sheath gas, auxiliary gas, and collision gas. The S-Lens RF Level was set to 90. MS spectra were acquired by full scan measurement in the range of m / z 300-2000 in positive mode. The acquired MS spectra were analyzed using Compound Discover 2.1 (Thermo Fisher Scientific Co., Ltd.). Glycosylation was detected by comparing with the O-linked glycan database. MS / MS spectra were acquired in a positive mode, data-dependently in Top10 mode, and analyzed using SimGlycan Software (PREMIER Biosoft International).

[0036] (2) Determination of the binding mode of O-linked glycans contained in human milk and pig stomach mucin materials In order to determine the linkage of N-acetylneuraminic acid in O-linked glycans contained in human milk and porcine stomach mucin materials, the samples were treated with either sialidase that specifically degrades α2,3 linkages or sialidase that degrades both α2,3 and α2,6 linkages, and then analyzed by LC / MS. In order to determine the linkage of fucose, the samples were treated with either fucosidase that specifically degrades α1,2 linkages, fucosidase that specifically degrades α1,3 and α1,4 linkages, or fucosidase that specifically degrades α1,2 linkages, α1,4 linkages, and α1,6 linkages, and then analyzed by LC / MS. Furthermore, to determine the binding mode of galactose, the samples were treated with either galactosidase that specifically degrades β1,3 bonds and fucosidase that specifically degrades α1,3 bonds and α1,4 bonds simultaneously, or galactosidase that specifically degrades β1,4 bonds simultaneously with fucosidase that specifically degrades α1,3 bonds and α1,4 bonds, and then analyzed by LC / MS. 27 μL of ultrapure water, 5 μL of the buffer solution provided with the enzyme, and 5 μL of the bovine serum albumin solution provided with the enzyme were added to 10 μL of 2-AB-labeled O-linked glycan solution prepared from breast milk or pig stomach mucin material, and then 3 μL of each enzyme solution was added and incubated at 37°C for 1 hour. The enzymes were inactivated by heating in boiling water for 5 minutes, and then subjected to LC / MS analysis. LC / MS analysis was performed as follows. HPLC was performed using UltiMate 3000, and MS was performed using Q-Exactive. The column used was GlycanPac AXH-1, and the column temperature was set to 40°C. The mobile phase used was acetonitrile (liquid A) and 50 mM ammonium formate aqueous solution (liquid B) adjusted to pH 4.4, and the flow rate was 0.4 mL / min. After sample introduction, the proportion of liquid B was linearly increased from 10% to 35% by 55 minutes, and then 35% of liquid B was passed from 55 minutes to 65 minutes. The spray voltage of the ESI probe was 3.5 kV, the capillary temperature was 275°C, and nitrogen gas was used for the sheath gas, auxiliary gas, and collision gas. The S-Lens RF Level was set to 90. The acquired MS spectrum was analyzed using FreeStyle software (Thermo Fisher Scientific Co., Ltd.).

[0037] 2.Results (1) Analysis of glycans of glycoproteins with Lewis X structures in breast milk Analysis of glycoprotein glycans with Lewis X structures in breast milk revealed that Neu5Acα2-3Galβ1-3[Galβ1-4(Fucα1-3)GlcNAcβ1-6]GalNAc (Lewis X glycan A) and Galβ1-4(Fucα1-3)GlcNAcβ1-3GalNAc (Lewis X glycan B). Therefore, these two types of Lewis X glycans in breast milk are expected to strengthen the intestinal barrier by enhancing TFF3 expression.

[0038] (2) Analysis of glycoprotein glycans with Lewis X structures contained in mucin material derived from porcine stomach Analysis of glycoprotein glycans with Lewis X structures contained in porcine stomach-derived mucin, a food material, revealed the detection of Lewis X glycan A. Therefore, porcine stomach-derived mucin, a food material, is expected to have the effect of strengthening the intestinal barrier through the enhancement of TFF3 expression due to the Lewis X glycans contained therein.

[0039] [Example 1] Preparation of mucin-containing milk powder 52.7 kg of whey powder, 239 kg of skim milk, and 32 g of mucin material derived from porcine stomach were dissolved in 500 kg of water, and this solution was mixed with 23.9 kg of vegetable oil and homogenized. The resulting solution was sterilized, concentrated and dried by a standard method to obtain 99 kg of milk powder. The milk powder was mixed with 1 kg of vitamin and mineral components to finally obtain 100 kg of modified milk powder. The amount of Lewis X sugar chain A in the obtained milk powder was 8.0 mg / 100 g solid.

[0040] [Example 2] Preparation of powdered milk containing glycopeptides 52.7 kg of whey powder, 239 kg of skim milk, and 250 mg of Lewis X sugar chain B powder were dissolved in 500 kg of water, and this solution was mixed with 23.9 kg of vegetable oil and homogenized. The resulting solution was sterilized, concentrated and dried by a standard method to obtain 99 kg of milk powder. The milk powder was mixed with 1 kg of vitamin and mineral components to finally obtain 100 kg of modified milk powder. The amount of Lewis X sugar chain B in the obtained milk powder was 0.25 mg / 100 g solid.

[0041] [Example 3] Preparation of Lewis X sugar chain blended milk powder 52.7 kg of whey powder, 239 kg of skim milk, and 250 mg of Lewis X trisaccharide were dissolved in 500 kg of water, and this solution was mixed with 23.9 kg of vegetable oil and homogenized. The resulting solution was sterilized, concentrated and dried by a conventional method to obtain 99 kg of milk powder. The milk powder was mixed with 1 kg of vitamin and mineral ingredients to finally obtain 100 kg of modified milk powder.

[0042] [Example 4] Preparation of sialyl Lewis X sugar chain blended milk powder 52.7 kg of whey powder, 239 kg of skim milk, and 250 mg of 3'-sialyl Lewis X were dissolved in 500 kg of water, and this solution was mixed with 23.9 kg of vegetable oil and homogenized. The resulting solution was sterilized, concentrated and dried by a conventional method to obtain 99 kg of milk powder. The milk powder was mixed with 1 kg of vitamin and mineral ingredients to finally obtain 100 kg of modified milk powder.

[0043] Example 5: Production of beverages The ingredients were mixed according to the composition shown in Table 2, filled into a container, and then heat sterilized to produce a beverage for preventing and / or improving allergies and autoimmune diseases of the present invention.

[0044] [Table 2] [Industrial Applicability]

[0045] According to the present invention, it is possible to provide a composition for enhancing TFF3 expression, which comprises, as an active ingredient, a sugar chain having a Lewis X structure and / or a sugar chain having a sialyl Lewis X structure.

Claims

1. A composition for enhancing TFF3 expression, comprising a sugar chain having a Lewis X structure and / or a sugar chain having a sialyl Lewis X structure as an active ingredient.

2. The composition for enhancing TFF3 expression according to claim 1 , wherein the sugar chain having a Lewis X structure is Lewis X trisaccharide.

3. The composition for enhancing TFF3 expression according to claim 1, wherein the sugar chain having a sialyl Lewis X structure is 3'-sialyl Lewis X or sialyl Lewis X lactose.

4. A pharmaceutical composition for enhancing TFF3 expression, a food composition for enhancing TFF3 expression, or a feed composition for enhancing TFF3 expression, comprising the composition for enhancing TFF3 expression described in any one of claims 1 to 3.

5. A composition for preventing and / or ameliorating an allergic disease, comprising a composition for enhancing TFF3 expression described in any one of claims 1 to 3.